an introduction to metabolismlibvolume3.xyz › civil › btech › semester4 › structural... ·...

LECTURE PRESENTATIONS

For CAMPBELL BIOLOGY, NINTH EDITION Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson

© 2011 Pearson Education, Inc.

Lectures by

Erin Barley

Kathleen Fitzpatrick

An Introduction to Metabolism

Chapter 8

Overview: The Energy of Life

• The living cell is a miniature chemical factory

where thousands of reactions occur

• The cell extracts energy and applies energy to

perform work

• Some organisms even convert energy to light,

as in bioluminescence


Figure 8.1

Concept 8.1: An organism’s metabolism

transforms matter and energy, subject to the

laws of thermodynamics

• Metabolism is the totality of an organism’s

chemical reactions

• Metabolism is an emergent property of life that

arises from interactions between molecules within

the cell


Organization of the Chemistry of Life into

Metabolic Pathways

• A metabolic pathway begins with a specific

molecule and ends with a product

• Each step is catalyzed by a specific enzyme


Figure 8.UN01

Enzyme 1 Enzyme 2 Enzyme 3

Reaction 1 Reaction 2 Reaction 3 Product Starting

molecule

A B C D

• Catabolic pathways release energy by

breaking down complex molecules into

simpler compounds

• Cellular respiration, the breakdown of glucose

in the presence of oxygen, is an example of a

pathway of catabolism


• Anabolic pathways consume energy to build

complex molecules from simpler ones

• The synthesis of protein from amino acids is an

example of anabolism

• Bioenergetics is the study of how organisms

manage their energy resources


Forms of Energy

• Energy is the capacity to cause change

• Energy exists in various forms, some of which

can perform work


• Kinetic energy is energy associated with motion

• Heat (thermal energy) is kinetic energy

associated with random movement of atoms or

molecules

• Potential energy is energy that matter possesses

because of its location or structure

• Chemical energy is potential energy available for release in a chemical reaction

• Energy can be converted from one form to another


Animation: Energy Concepts

Figure 8.2 A diver has more potential energy on the platform than in the water.

Diving converts potential energy to kinetic energy.

Climbing up converts the kinetic energy of muscle movement to potential energy.

A diver has less potential energy in the water than on the platform.

The Laws of Energy Transformation

• Thermodynamics is the study of energy

transformations

• A isolated system, such as that approximated by

liquid in a thermos, is isolated from its

surroundings

• In an open system, energy and matter can be

transferred between the system and its

surroundings

• Organisms are open systems


The First Law of Thermodynamics

• According to the first law of thermodynamics,

the energy of the universe is constant

– Energy can be transferred and transformed,

but it cannot be created or destroyed

• The first law is also called the principle of

conservation of energy


The Second Law of Thermodynamics

• During every energy transfer or transformation,

some energy is unusable, and is often lost as

heat

• According to the second law of thermodynamics

– Every energy transfer or transformation increases the entropy (disorder) of the universe


Figure 8.3

(a) First law of thermodynamics (b) Second law of thermodynamics

Chemical energy

Heat

Figure 8.3a

(a) First law of thermodynamics

Chemical energy

Figure 8.3b

(b) Second law of thermodynamics

Heat

• Living cells unavoidably convert organized

forms of energy to heat

• Spontaneous processes occur without

energy input; they can happen quickly or

slowly

• For a process to occur without energy input, it

must increase the entropy of the universe


Biological Order and Disorder

• Cells create ordered structures from less

ordered materials

• Organisms also replace ordered forms of

matter and energy with less ordered forms

• Energy flows into an ecosystem in the form

of light and exits in the form of heat


Figure 8.4

Figure 8.4a

Figure 8.4b

• The evolution of more complex organisms does

not violate the second law of thermodynamics

• Entropy (disorder) may decrease in an

organism, but the universe’s total entropy

increases


Concept 8.2: The free-energy change of a

reaction tells us whether or not the reaction

occurs spontaneously

• Biologists want to know which reactions occur

spontaneously and which require input of

energy

• To do so, they need to determine energy

changes that occur in chemical reactions


Free-Energy Change, ∆∆∆∆G

• A living system’s free energy is energy that

can do work when temperature and pressure

are uniform, as in a living cell


• The change in free energy (∆G) during a

process is related to the change in enthalpy, or

change in total energy (∆H), change in entropy

(∆S), and temperature in Kelvin (T)

∆G = ∆H – T∆S

• Only processes with a negative ∆G are

spontaneous

• Spontaneous processes can be harnessed to

perform work


Free Energy, Stability, and Equilibrium

• Free energy is a measure of a system’s

instability, its tendency to change to a more

stable state

• During a spontaneous change, free energy

decreases and the stability of a system

increases

• Equilibrium is a state of maximum stability

• A process is spontaneous and can perform

work only when it is moving toward equilibrium


Figure 8.5

• More free energy (higher G) • Less stable • Greater work capacity

In a spontaneous change • The free energy of the system decreases (∆∆∆∆G <<<< 0) • The system becomes more stable • The released free energy can be harnessed to do work

• Less free energy (lower G) • More stable • Less work capacity

(a) Gravitational motion (b) Diffusion (c) Chemical reaction

Figure 8.5a

• More free energy (higher G) • Less stable • Greater work capacity

In a spontaneous change • The free energy of the system decreases (∆∆∆∆G <<<< 0) • The system becomes more stable • The released free energy can be harnessed to do work

• Less free energy (lower G) • More stable • Less work capacity

Figure 8.5b

(a) Gravitational motion (b) Diffusion (c) Chemical reaction

Free Energy and Metabolism

• The concept of free energy can be applied to

the chemistry of life’s processes


Exergonic and Endergonic Reactions in

Metabolism

• An exergonic reaction proceeds with a net

release of free energy and is spontaneous

• An endergonic reaction absorbs free energy

from its surroundings and is nonspontaneous


Figure 8.6 (a) Exergonic reaction: energy released, spontaneous

(b) Endergonic reaction: energy required, nonspontaneous

Reactants

Energy

Products

Progress of the reaction

Amount of energy released (∆∆∆∆G <<<< 0)

Reactants

Energy

Products

Amount of energy required (∆∆∆∆G >>>> 0)


Free energy

Free energy

Figure 8.6a

(a) Exergonic reaction: energy released, spontaneous

Reactants

Energy

Products


Amount of energy released (∆∆∆∆G <<<< 0)

Free energy

Figure 8.6b

(b) Endergonic reaction: energy required, nonspontaneous

Reactants

Energy

Products

Amount of energy required (∆∆∆∆G >>>> 0)


Free energy

Equilibrium and Metabolism

• Reactions in a closed system eventually reach

equilibrium and then do no work

• Cells are not in equilibrium; they are open

systems experiencing a constant flow of materials

• A defining feature of life is that metabolism is

never at equilibrium

• A catabolic pathway in a cell releases free energy

in a series of reactions

• Closed and open hydroelectric systems can

serve as analogies


Figure 8.7

(a) An isolated hydroelectric system

(b) An open hydroelectric system

(c) A multistep open hydroelectric system

∆∆∆∆G <<<< 0

∆∆∆∆G <<<< 0

∆∆∆∆G <<<< 0 ∆∆∆∆G <<<< 0

∆∆∆∆G <<<< 0

∆∆∆∆G ==== 0

Figure 8.7a

(a) An isolated hydroelectric system

∆∆∆∆G <<<< 0 ∆∆∆∆G ==== 0

Figure 8.7b

(b) An open hydroelectric system

∆∆∆∆G <<<< 0

Figure 8.7c

(c) A multistep open hydroelectric system

∆∆∆∆G <<<< 0

∆∆∆∆G <<<< 0

∆∆∆∆G <<<< 0

Concept 8.3: ATP powers cellular work by

coupling exergonic reactions to endergonic

reactions

• A cell does three main kinds of work

– Chemical

– Transport

– Mechanical

• To do work, cells manage energy resources by

energy coupling, the use of an exergonic

process to drive an endergonic one

• Most energy coupling in cells is mediated by ATP


The Structure and Hydrolysis of ATP

• ATP (adenosine triphosphate) is the cell’s

energy shuttle

• ATP is composed of ribose (a sugar), adenine

(a nitrogenous base), and three phosphate

groups


Figure 8.8

(a) The structure of ATP

Phosphate groups

Adenine

Ribose

Adenosine triphosphate (ATP)

Energy

Inorganic phosphate

Adenosine diphosphate (ADP)

(b) The hydrolysis of ATP

Figure 8.8a

(a) The structure of ATP

Phosphate groups

Adenine

Ribose

Figure 8.8b

Adenosine triphosphate (ATP)

Energy

Inorganic phosphate

Adenosine diphosphate (ADP)

(b) The hydrolysis of ATP

• The bonds between the phosphate groups

of ATP’s tail can be broken by hydrolysis

• Energy is released from ATP when the

terminal phosphate bond is broken

• This release of energy comes from the

chemical change to a state of lower free

energy, not from the phosphate bonds

themselves


How the Hydrolysis of ATP Performs Work

• The three types of cellular work (mechanical,

transport, and chemical) are powered by the

hydrolysis of ATP

• In the cell, the energy from the exergonic

reaction of ATP hydrolysis can be used to

drive an endergonic reaction

• Overall, the coupled reactions are exergonic


Figure 8.9

Glutamic acid

Ammonia Glutamine

(b) Conversion reaction coupled with ATP hydrolysis

Glutamic acid conversion to glutamine

(a)

(c) Free-energy change for coupled reaction

Glutamic acid

Glutamine Phosphorylated intermediate

Glu

NH3 NH2

Glu ∆∆∆∆GGlu = +3.4 kcal/mol

ATP ADP ADP

NH3

Glu Glu

P P i

P i ADP

Glu

NH2

∆∆∆∆GGlu = +3.4 kcal/mol

Glu Glu

NH3 NH2 ATP

∆∆∆∆GATP = −−−−7.3 kcal/mol ∆∆∆∆GGlu = +3.4 kcal/mol

+ ∆∆∆∆GATP = −−−−7.3 kcal/mol

Net ∆∆∆∆G = −−−−3.9 kcal/mol

1 2

• ATP drives endergonic reactions by

phosphorylation, transferring a phosphate

group to some other molecule, such as a

reactant

• The recipient molecule is now called a

phosphorylated intermediate


Figure 8.10 Transport protein Solute

ATP

P P i

P i ADP

P i ADP ATP ATP

Solute transported

Vesicle Cytoskeletal track

Motor protein Protein and vesicle moved

(b) Mechanical work: ATP binds noncovalently to motor proteins and then is hydrolyzed.

(a) Transport work: ATP phosphorylates transport proteins.

The Regeneration of ATP

• ATP is a renewable resource that is

regenerated by addition of a phosphate

group to adenosine diphosphate (ADP)

• The energy to phosphorylate ADP comes

from catabolic reactions in the cell

• The ATP cycle is a revolving door through

which energy passes during its transfer from

catabolic to anabolic pathways


Figure 8.11

Energy from

catabolism (exergonic,

energy-releasing

processes)

Energy for cellular

work (endergonic,

energy-consuming

processes)

ATP

ADP P i

H2O

Concept 8.4: Enzymes speed up metabolic

reactions by lowering energy barriers

• A catalyst is a chemical agent that speeds up

a reaction without being consumed by the

reaction

• An enzyme is a catalytic protein

• Hydrolysis of sucrose by the enzyme sucrase

is an example of an enzyme-catalyzed

reaction


Figure 8.UN02

Sucrase

Sucrose

(C12H22O11)

Glucose

(C6H12O6)

Fructose

(C6H12O6)

The Activation Energy Barrier

• Every chemical reaction between molecules

involves bond breaking and bond forming

• The initial energy needed to start a chemical

reaction is called the free energy of activation,

or activation energy (EA)

• Activation energy is often supplied in the form

of thermal energy that the reactant molecules

absorb from their surroundings


Figure 8.12

Transition state

Reactants

Products


Free energy

EA

∆∆∆∆G <<<< O

A B

C D

A B

C D

A B

C D

How Enzymes Lower the EA Barrier

• Enzymes catalyze reactions by lowering the EA

barrier

• Enzymes do not affect the change in free

energy (∆G); instead, they hasten reactions

that would occur eventually


Animation: How Enzymes Work

Figure 8.13

Course of reaction without enzyme

EA

without

enzyme EA with enzyme is lower

Course of reaction with enzyme

Reactants

Products

∆∆∆∆G is unaffected by enzyme


Free energy

Substrate Specificity of Enzymes

• The reactant that an enzyme acts on is called the

enzyme’s substrate

• The enzyme binds to its substrate, forming an

enzyme-substrate complex

• The active site is the region on the enzyme

where the substrate binds

• Induced fit of a substrate brings chemical

groups of the active site into positions that

enhance their ability to catalyze the reaction


Figure 8.14

Substrate

Active site

Enzyme Enzyme-substrate complex

(a) (b)

Catalysis in the Enzyme’s Active Site

• In an enzymatic reaction, the substrate binds to

the active site of the enzyme

• The active site can lower an EA barrier by

– Orienting substrates correctly

– Straining substrate bonds

– Providing a favorable microenvironment

– Covalently bonding to the substrate


Figure 8.15-1

Substrates

Substrates enter active site.

Enzyme-substrate complex

Substrates are held in active site by weak interactions.

1 2

Enzyme

Active site

Figure 8.15-2

Substrates




Active site can lower EA and speed up a reaction.

1 2

3

Substrates are converted to products.

4

Enzyme

Active site

Figure 8.15-3

Substrates



Enzyme

Products


Active site can lower EA and speed up a reaction.

Active site is

available for two new substrate molecules.

Products are released.

Substrates are converted to products.

1 2

3

4 5

6

Effects of Local Conditions on Enzyme

Activity

• An enzyme’s activity can be affected by

– General environmental factors, such as

temperature and pH

– Chemicals that specifically influence the

enzyme


Effects of Temperature and pH

• Each enzyme has an optimal temperature in

which it can function

• Each enzyme has an optimal pH in which it can

function

• Optimal conditions favor the most active shape

for the enzyme molecule


Figure 8.16

Optimal temperature for typical human enzyme (37°°°°C)

Optimal temperature for

enzyme of thermophilic

(heat-tolerant)

bacteria (77°°°°C)

Temperature (°°°°C)

(a) Optimal temperature for two enzymes

Rate of reaction

Rate of reaction

120 100 80 60 40 20 0

0 1 2 3 4 5 6 7 8 9 10 pH

(b) Optimal pH for two enzymes

Optimal pH for pepsin (stomach enzyme)

Optimal pH for trypsin (intestinal enzyme)

Figure 8.16a

Optimal temperature for typical human enzyme (37°°°°C)

Optimal temperature for enzyme of thermophilic

(heat-tolerant) bacteria (77°°°°C)

Temperature (°°°°C)

(a) Optimal temperature for two enzymes

Rate of reaction

120 100 80 60 40 20 0

Figure 8.16b

Rate of reaction

0 1 2 3 4 5 6 7 8 9 10 pH

(b) Optimal pH for two enzymes

Optimal pH for pepsin (stomach enzyme)

Optimal pH for trypsin (intestinal enzyme)

Cofactors

• Cofactors are nonprotein enzyme helpers

• Cofactors may be inorganic (such as a metal in

ionic form) or organic

• An organic cofactor is called a coenzyme

• Coenzymes include vitamins


Enzyme Inhibitors

• Competitive inhibitors bind to the active site

of an enzyme, competing with the substrate

• Noncompetitive inhibitors bind to another

part of an enzyme, causing the enzyme to

change shape and making the active site less

effective

• Examples of inhibitors include toxins, poisons,

pesticides, and antibiotics


Figure 8.17

(a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition

Substrate

Active site

Enzyme

Competitive inhibitor

Noncompetitive inhibitor

The Evolution of Enzymes

• Enzymes are proteins encoded by genes

• Changes (mutations) in genes lead to changes

in amino acid composition of an enzyme

• Altered amino acids in enzymes may alter their

substrate specificity

• Under new environmental conditions a novel

form of an enzyme might be favored


Figure 8.18

Two changed amino acids were found near the active site.

Active site

Two changed amino acids were found in the active site.

Two changed amino acids were found on the surface.

Concept 8.5: Regulation of enzyme activity

helps control metabolism

• Chemical chaos would result if a cell’s

metabolic pathways were not tightly regulated

• A cell does this by switching on or off the

genes that encode specific enzymes or by

regulating the activity of enzymes


Allosteric Regulation of Enzymes

• Allosteric regulation may either inhibit or

stimulate an enzyme’s activity

• Allosteric regulation occurs when a regulatory

molecule binds to a protein at one site and

affects the protein’s function at another site


Allosteric Activation and Inhibition

• Most allosterically regulated enzymes are

made from polypeptide subunits

• Each enzyme has active and inactive forms

• The binding of an activator stabilizes the

active form of the enzyme

• The binding of an inhibitor stabilizes the

inactive form of the enzyme


Figure 8.19

Regulatory site (one of four)

(a) Allosteric activators and inhibitors

Allosteric enzyme with four subunits

Active site (one of four)

Active form

Activator

Stabilized active form

Oscillation

Non- functional active site

Inactive form Inhibitor

Stabilized inactive form

Inactive form

Substrate


(b) Cooperativity: another type of allosteric activation

Figure 8.19a

Regulatory site (one of four)

(a) Allosteric activators and inhibitors

Allosteric enzyme with four subunits

Active site (one of four)

Active form

Activator


Oscillation

Nonfunctional active site

Inactive form Inhibitor

Stabilized inactive form

Figure 8.19b

Inactive form

Substrate


(b) Cooperativity: another type of allosteric activation

• Cooperativity is a form of allosteric regulation

that can amplify enzyme activity

• One substrate molecule primes an enzyme to

act on additional substrate molecules more

readily

• Cooperativity is allosteric because binding by a

substrate to one active site affects catalysis in

a different active site


Identification of Allosteric Regulators

• Allosteric regulators are attractive drug

candidates for enzyme regulation because of

their specificity

• Inhibition of proteolytic enzymes called

caspases may help management of

inappropriate inflammatory responses


Figure 8.20

Caspase 1 Active site

Substrate

SH SH

SH

Known active form Active form can bind substrate

Allosteric binding site

Allosteric inhibitor

Hypothesis: allosteric inhibitor locks enzyme in inactive form

Caspase 1

Active form Allosterically inhibited form

Inhibitor

Inactive form

EXPERIMENT

RESULTS

Known inactive form

Figure 8.20a

Caspase 1 Active site

Substrate

SH SH

SH

Known active form Active form can

bind substrate

Allosteric

binding site Allosteric

inhibitor Hypothesis: allosteric

inhibitor locks enzyme

in inactive form

EXPERIMENT

Known inactive form

Figure 8.20b

Caspase 1

Active form Allosterically

inhibited form

Inhibitor

Inactive form

RESULTS

Feedback Inhibition

• In feedback inhibition, the end product of a

metabolic pathway shuts down the pathway

• Feedback inhibition prevents a cell from

wasting chemical resources by synthesizing

more product than is needed


Figure 8.21

Active site available

Isoleucine used up by

cell

Feedback inhibition

Active site of enzyme 1 is

no longer able

to catalyze the

conversion

of threonine to intermediate A;

pathway is

switched off. Isoleucine binds to

allosteric

site.

Initial substrate

(threonine)

Threonine in active site

Enzyme 1 (threonine

deaminase)

Intermediate A

Intermediate B

Intermediate C

Intermediate D

Enzyme 2

Enzyme 3

Enzyme 4

Enzyme 5

End product (isoleucine)

Specific Localization of Enzymes Within

the Cell

• Structures within the cell help bring order to

metabolic pathways

• Some enzymes act as structural components

of membranes

• In eukaryotic cells, some enzymes reside in

specific organelles; for example, enzymes for

cellular respiration are located in mitochondria


Figure 8.22

Mitochondria

The matrix contains enzymes in solution that are involved in one stage

of cellular respiration.

Enzymes for another stage of cellular respiration are

embedded in the inner membrane.

1 µµµµm

Figure 8.22a

1 µµµµm

Figure 8.UN03

Course of reaction without enzyme

EA without enzyme EA with

enzyme is lower

Course of reaction with enzyme

Reactants

Products

∆∆∆∆G is unaffected by enzyme


Free energy

Figure 8.UN04

Figure 8.UN05

Figure 8.UN06

Figure 8.UN07

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